Malaria continues one of the greatest major disease problems in the world. Mosquito eradication programs have failed for a variety of reasons including economic, climatic and insecticide resistance. Moreover, chloroquine-resistant strains of P. falciparum have appeared in Southeast and South America. Progress in the control of the disease will require (1) improved culture of the parasites; (2) clarification of host-cell invasion processes; and (3) elucidation of host-cell surface modifications that are perhaps essential for intracellular survival. The study of Ca 2 ions metabolism in infected erythrocytes is necessary to achieve these goals since Ca 2 ions is known to be involved in the deformability of the erythrocyte membrane and regulation of cellular metabolic processes and is a critical variable in cell tissue culture. We therefore plan a program for the detailed quantitative study of Ca 2 ions metabolism in P. knowlesi-infected monkey erythrocytes. To answer the questions inherent in this project we propose three interlocking approaches: (a) a detailed quantitative comparison of Ca 2 ions binding and uptake by normal and infected erythrocytes including measurements of absolute amounts of Ca 2 ions and determination of influx and efflux rates under different physiological conditions, (b) a qualtative description of Ca 2 ions-membrane interactions by employing the spectroscopic properties of lanthanides, specific chemical and enzymatic procedures, and radioactive Ca 2 ions and lanthanide binding studies. Intact cells and purified membrane fractions will be used. We will devote considerable effort into the characterization of Ca 2 ions -ATPase activity in different membrane fractions of the infected erythrocyte. (c) study the effect of Ca 2 ions on a key membrane function, selective permeability, by monitoring the membrane potential. In addition, Ca ions induced alterations of membrane protein proximity relationships in Plasmodia-infected erythrocytes will be studied.